- A new study suggests that a higher intake of N-glycolylneuraminic acid (Neu5Gc), a sugar present in red meat, is associated with a higher relative risk of developing type 2 diabetes.
- The relationship remained statistically significant after adjusting for various factors, such as age, sex, physical activity, overall diet, smoking, and existing health conditions.
- While Neu5Gc is also found in some dairy products, the link with total dietary Neu5Gc appeared to be largely driven by meat-derived Neu5Gc.
- However, the study was observational and preliminary, meaning it does not prove cause and effect.
Diet is an important modifiable factor in the development of type 2 diabetes, with dietary patterns high in red and processed meat, and sugar-sweetened foods and drinks generally being associated with greater risk.
In particular, studies have consistently reported an
One proposed mechanism linking red meat consumption to diabetes is the presence of a sugar known as N-glycolylneuraminic acid (Neu5Gc), which is naturally produced by most mammals and can be found in some foods, particularly red meat such as beef and lamb, and to a lesser extent in dairy products.
Because Neu5Gc is foreign to the human body, the immune system can produce antibodies against it, which may promote inflammation and could lead to insulin resistance.
Now, preliminary findings presented at the Annual Meeting of the European Association for the Study of Diabetes (EASD) in Milan, Italy, report an association between higher dietary Neu5Gc intake and increased risk of developing diabetes.
Notably, the researchers found that people with the highest estimated dietary intake of Neu5Gc from meat had a 63% higher risk of developing type 2 diabetes than those with the lowest intake.
However, the researchers stress that the findings are preliminary, based on an observational study, and have not yet been peer-reviewed, so they cannot establish that Neu5Gc or red meat directly causes type 2 diabetes.
Higher Neu5Gc intake associated with greater diabetes risk
The researchers analyzed data from 89,953 adults participating in the NutriNet-Santé study, a large French prospective observational cohort that examines relationships between diet, lifestyle, and health. Participants were, on average, 42 years old, and 79% were female. None had type 2 diabetes or cancer when they entered the study.
Dietary intake was assessed using three 24-hour dietary records. Researchers then estimated participants’ Neu5Gc consumption using a database that contains measurements of the compound in various foods. Participants were divided into 5 groups according to their estimated intake of meat-derived Neu5Gc.
During a median follow-up of 7.2 years, 966 participants developed type 2 diabetes. Compared with people in the lowest Neu5Gc-intake group, those in the highest groups showed statistically significant associations with type 2 diabetes.
Notably, the highest group had a 63% higher relative risk of developing type 2 diabetes, while the second-highest group had a 41% higher risk, according to a press release.
The researchers observed the association in both males and females, although the study was not designed to establish a difference in risk between the sexes.
“This is a relative risk: people in the top fifth of meat-derived Neu5Gc intake had a 63% higher risk than those in the bottom fifth, after accounting for many other factors,” lead author Leopold Fezeu, MD, PhD, from the Université Sorbonne Paris Nord, Bobigny, France, explained to Medical News Today.
“It does not mean that 63% of high consumers will develop diabetes. In our cohort, type 2 diabetes remained relatively uncommon over about seven years of follow-up, so the absolute difference in risk for any individual is much smaller than the relative figure suggests. It is also worth noting that the risk did not increase even: it rose mainly in the two highest intake groups.”
—Leopold Fezeu, MD, PhD
Could inflammation explain the association?
The researchers suggest that chronic inflammation could be one possible biological explanation.
When Neu5Gc is incorporated into human tissues, the immune system recognizes Neu5Gc as foreign and produces antibodies against it. This inflammatory response is known as xenosialitis.
Repeated exposure could therefore contribute to persistent immune activation. Chronic inflammation is already thought to play a role in insulin resistance and the development of type 2 diabetes.
The findings of the preliminary study suggest that inflammation may help explain the relationship between red meat consumption and type 2 diabetes.
“It is a plausible explanation, but it remains a hypothesis,” Fezeu noted. “Humans cannot produce Neu5Gc, yet it is absorbed from red meat and incorporated into our tissues, where the immune system recognizes it as foreign.”
“The resulting low-grade chronic inflammation, called xenosialitis, could impair insulin action and the insulin-producing cells of the pancreas. Our findings are consistent with this mechanism: only about 13% of the association was explained by weight gain.”
—Leopold Fezeu, MD, PhD
“However, we did not measure anti-Neu5Gc antibodies in this study, so we could not test the mechanism directly. This is an important next step,” Fezeu added.
Link weakens after accounting for red meat intake
An important finding was that the relationship became weaker and was no longer statistically significant after the researchers adjusted for total red meat consumption. This means the study cannot establish that Neu5Gc itself is responsible for the observed association.
Red meat contains numerous compounds that could potentially affect diabetes risk, including haem iron and other nutrients and food components. Therefore, the researchers suggest that Neu5Gc may explain part of the relationship between red meat consumption and type 2 diabetes, but other components of red meat could also contribute.
The study also found no significant association between Neu5Gc from dairy products and type 2 diabetes. According to the researchers, this may partly reflect differences in Neu5Gc concentrations among foods, as well as in typical serving sizes.
When Neu5Gc from all dietary sources was considered together, people in the highest intake group had a 37% higher risk of developing type 2 diabetes than those in the lowest group. The researchers said this association was largely driven by Neu5Gc from meat.
“Neu5Gc and red meat are closely linked, since red meat is the main source of Neu5Gc, so it is difficult to fully separate their effects,” Fezeu said.
What role did body weight play?
The researchers estimated that obesity accounted for approximately 13% of the association between meat-derived Neu5Gc and type 2 diabetes. This suggests that, if the association is confirmed, body weight may explain only part of the relationship.
The researchers propose that inflammatory effects on insulin-producing cells and on tissues involved in insulin sensitivity could be among the mechanisms. However, this remains a hypothesis that requires further testing.
Importantly, the study does not show that consuming a particular amount of red meat will cause diabetes.
People in the highest Neu5Gc-intake group generally consumed more red meat than those in the lowest group. Among males, median red meat intake ranged from 5 grams (g) per day in the lowest group to 97g per day in the highest. Among females, it ranged from 0 to 73g per day.
These figures describe the dietary patterns of people in the different study groups and should not be interpreted as safe or harmful thresholds for meat consumption.
More research is necessary
While the results may suggest a mechanism for the possible link between red meat and diabetes, the researchers emphasize several limitations.
First, the findings are preliminary and have not yet been independently validated. The estimates could change as the analysis is finalized.
Second, because the study is observational, it cannot determine whether Neu5Gc exposure causes type 2 diabetes. Even though researchers adjusted for a range of potential confounding factors, other lifestyle, environmental, or social factors that were not measured could have influenced the results.
Dietary intake was also estimated from participants’ dietary records rather than continuously measured throughout the follow-up period. Changes in dietary patterns over time could therefore have introduced some measurement error.
Finally, the study did not directly measure anti-Neu5Gc antibodies, meaning it could not directly demonstrate that the proposed immune mechanism occurred in participants who developed diabetes.
The researchers plan to investigate how Neu5Gc interacts with other components of red meat, including haem iron, and to measure anti-Neu5Gc antibodies in future studies.
Further research could also examine whether replacing foods particularly high in Neu5Gc, such as beef and lamb, with poultry or plant-based protein sources affects type 2 diabetes risk.
“If our findings are confirmed, this would be a logical hypothesis to test, since poultry and plant foods contain little or no Neu5Gc, whereas beef and lamb are among the richest sources,” Fezeu told MNT.
Could swapping red meat for plants help lower risk?
“(W)e did not study food substitutions, so we cannot say that such a change would reduce diabetes risk. In the meantime, current dietary guidelines already recommend limiting red meat intake, for reasons that go beyond Neu5Gc.”
—Leopold Fezeu, MD, PhD
“As a final remark, this is an observational study: it shows an association, not cause and effect, and residual confounding cannot be excluded. Our findings need to be confirmed in other populations, ideally with direct measurement of anti-Neu5Gc antibodies,” Fezeu concluded.
